Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model

Epilepsy is a chronic disease of the brain that affects over 65 million people worldwide. Acquired epilepsy is initiated by neurological insults, such as status epilepticus, which can result in the generation of ROS and induction of oxidative stress. Suppressing oxidative stress by upregulation of t...

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Autores principales:	Sereen Sandouka, Tawfeeq Shekh-Ahmad
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	epilepsy epileptogenesis Nrf2-KEAP1 pathway oxidative stress SFN Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/810c097acb5b4dccbdc6b5637129d867
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spelling	oai:doaj.org-article:810c097acb5b4dccbdc6b5637129d8672021-11-25T16:26:35ZInduction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model10.3390/antiox101117022076-3921https://doaj.org/article/810c097acb5b4dccbdc6b5637129d8672021-10-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1702https://doaj.org/toc/2076-3921Epilepsy is a chronic disease of the brain that affects over 65 million people worldwide. Acquired epilepsy is initiated by neurological insults, such as status epilepticus, which can result in the generation of ROS and induction of oxidative stress. Suppressing oxidative stress by upregulation of the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown to be an effective strategy to increase endogenous antioxidant defences, including in brain diseases, and can ameliorate neuronal damage and seizure occurrence in epilepsy. Here, we aim to test the neuroprotective potential of a naturally occurring Nrf2 activator sulforaphane, in in vitro epileptiform activity model and a temporal lobe epilepsy rat model. Sulforaphane significantly decreased ROS generation during epileptiform activity, restored glutathione levels, and prevented seizure-like activity-induced neuronal cell death. When given to rats after 2 h of kainic acid-induced status epilepticus, sulforaphane significantly increased the expression of Nrf2 and related antioxidant genes, improved oxidative stress markers, and increased the total antioxidant capacity in both the plasma and hippocampus. In addition, sulforaphane significantly decreased status epilepticus-induced neuronal cell death. Our results demonstrate that Nrf2 activation following an insult to the brain exerts a neuroprotective effect by reducing neuronal death, increasing the antioxidant capacity, and thus may also modify epilepsy development.Sereen SandoukaTawfeeq Shekh-AhmadMDPI AGarticleepilepsyepileptogenesisNrf2-KEAP1 pathwayoxidative stressSFNTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1702, p 1702 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	epilepsy epileptogenesis Nrf2-KEAP1 pathway oxidative stress SFN Therapeutics. Pharmacology RM1-950
spellingShingle	epilepsy epileptogenesis Nrf2-KEAP1 pathway oxidative stress SFN Therapeutics. Pharmacology RM1-950 Sereen Sandouka Tawfeeq Shekh-Ahmad Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model
description	Epilepsy is a chronic disease of the brain that affects over 65 million people worldwide. Acquired epilepsy is initiated by neurological insults, such as status epilepticus, which can result in the generation of ROS and induction of oxidative stress. Suppressing oxidative stress by upregulation of the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown to be an effective strategy to increase endogenous antioxidant defences, including in brain diseases, and can ameliorate neuronal damage and seizure occurrence in epilepsy. Here, we aim to test the neuroprotective potential of a naturally occurring Nrf2 activator sulforaphane, in in vitro epileptiform activity model and a temporal lobe epilepsy rat model. Sulforaphane significantly decreased ROS generation during epileptiform activity, restored glutathione levels, and prevented seizure-like activity-induced neuronal cell death. When given to rats after 2 h of kainic acid-induced status epilepticus, sulforaphane significantly increased the expression of Nrf2 and related antioxidant genes, improved oxidative stress markers, and increased the total antioxidant capacity in both the plasma and hippocampus. In addition, sulforaphane significantly decreased status epilepticus-induced neuronal cell death. Our results demonstrate that Nrf2 activation following an insult to the brain exerts a neuroprotective effect by reducing neuronal death, increasing the antioxidant capacity, and thus may also modify epilepsy development.
format	article
author	Sereen Sandouka Tawfeeq Shekh-Ahmad
author_facet	Sereen Sandouka Tawfeeq Shekh-Ahmad
author_sort	Sereen Sandouka
title	Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model
title_short	Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model
title_full	Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model
title_fullStr	Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model
title_full_unstemmed	Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model
title_sort	induction of the nrf2 pathway by sulforaphane is neuroprotective in a rat temporal lobe epilepsy model
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/810c097acb5b4dccbdc6b5637129d867
work_keys_str_mv	AT sereensandouka inductionofthenrf2pathwaybysulforaphaneisneuroprotectiveinarattemporallobeepilepsymodel AT tawfeeqshekhahmad inductionofthenrf2pathwaybysulforaphaneisneuroprotectiveinarattemporallobeepilepsymodel
_version_	1718413147908341760

Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model

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